There has been an increased interest in the area of controlled crystal formation in the pharmaceutical industry; particularly in the area of crystal polymorphism and solid form purity (see Brittain, H. G., Effects of mechanical processing on phase composition. Journal of Pharmaceutical Sciences 2002, 91, (7), 1573-1580). Typically, the synthesized drugs are crystallized in the purest form possible and marketed in the forms of pills, tablets, etc.
In addition, crystallization is also used for understanding the molecular structures and interactions of proteins to develop new drug treatments that target specific human, animal, and plant diseases (see Roberts, M. M.; Heng, J. Y. Y.; Williams, D. R., Protein Crystallization by Forced Flow through Glass Capillaries: Enhanced Lysozyme Crystal Growth. Crystal Growth & Design 2010, 10, (3), 1074-1083).
In particular, crystallography has become a very useful tool for scientists in recent years due to its success in contributing to the understanding of molecular structures. While crystals of all molecular types are helping to recognize biological significances, proteins and amino acids are the primary molecules that are being focused on today. Amino acids are of particular importance because of their solubility and stabilizing properties that allow them to create multitudes of distinctive proteins (see Ito, L.; Kobayashi, T.; Shiraki, K.; Yamaguchi, H., Effect of amino acids and amino acid derivatives on crystallization of hemoglobin and ribonuclease A. Journal of Synchrotron Radiation 2008, 15, 316-318). Along with this, they also can serve as either intermediate or end products of biological functions, and have a wide range of applications in the chemical, food, cosmetic, and pharmaceutical industries (see Ng, K. M.; Harjo, B.; Wibowo, C., Development of amino acid crystallization processes: L-glutamic acid. Industrial & Engineering Chemistry Research 2007, 46, (9), 2814-2822).
One can find numerous studies related to crystallization of small molecules in the literature. For example, Myerson and co-workers have been employing polarized laser light irradiation for the crystallization of different polymorphs of glycine (see Garetz, B. A.; Matic, J.; Myerson, A. S., Polarization switching of crystal structure in the nonphotochemical light-induced nucleation of supersaturated aqueous glycine solutions. Physical Review Letters 2002, 89, (17), 175501). The same group also has demonstrated the use of self-assembled monolayers (SAMs) of alkane thiols on patterned gold thin films for size-controlled crystallization of glycine molecules through solvent evaporation (see Lee, A. Y.; Lee, I. S.; Dettet, S. S.; Boerner, J.; Myerson, A. S., Crystallization on confined engineered surfaces: A method to control crystal size and generate different polymorphs. Journal of the American Chemical Society 2005, 127, (43), 14982-14983). Ward and coworkers have employed nanoscale cylindrical pores to control the orientation of crystals formed by stereochemical inhibition (see Hamilton, B. D.; Weissbuch, I.; Lahav, M.; Hillmyer, M. A.; Ward, M. D., Manipulating Crystal Orientation in Nanoscale Cylindrical Pores by Stereochemical Inhibition. Journal of the American Chemical Society 2009, 131, (7), 2588-2596). Zukoski and co-workers have demonstrated the selective growth of γ-glycine crystals via concentrating micro-droplets of aqueous glycine solutions through slow evaporation-based crystallization platform (see He, G. W.; Bhamidi, V.; Wilson, S. R.; Tan, R. B. H.; Kenis, P. J. A.; Zukoski, C. F., Direct growth of gamma-glycine from neutral aqueous solutions by slow, evaporation-driven crystallization. Crystal Growth & Design 2006, 6, (8), 1746-1749).
In these reports, it was shown that the rapid evaporation of solvent produces the unstable β-form of glycine, while slowing the evaporation of solvent produced the kinetically stable α-form. Moreover, the generation of very slow super-saturation from water results in the stable γ-form (see He, G. W.; Bhamidi, V.; Wilson, S. R.; Tan, R. B. H.; Kenis, P. J. A.; Zukoski, C. F., Direct growth of gamma-glycine from neutral aqueous solutions by slow, evaporation-driven crystallization. Crystal Growth & Design 2006, 6, (8), 1746-1749). It was also shown that the distribution of glycine crystals can be affected by the surface (SAMs, polymers, etc.) as well as by the solution pH (see He, G. W.; Bhamidi, V.; Wilson, S. R.; Tan, R. B. H.; Kenis, P. J. A.; Zukoski, C. F., Direct growth of gamma-glycine from neutral aqueous solutions by slow, evaporation-driven crystallization. Crystal Growth & Design 2006, 6, (8), 1746-1749).
However, no techniques exist for the rapid (i.e., in a matter of seconds) and selective formation of crystals, e.g., the stable α- and γ-forms of glycine, without using additives, SAMs of alkane thiols or other engineered surfaces.